S0356 Oxaliplatin, 5-FU, Radiation Therapy (RT), Surgery for Pts With Stage II or III Cancer of Esophagus or Gastroesophageal (GE) Junction

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT00086996
First received: July 8, 2004
Last updated: September 4, 2013
Last verified: September 2013
  Purpose

RATIONALE: Drugs used in chemotherapy, such as oxaliplatin and fluorouracil, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Oxaliplatin and fluorouracil may make tumor cells more sensitive to radiation therapy and may kill more tumor cells. Giving chemotherapy and radiation therapy before surgery may shrink the tumor so that it can be removed.

PURPOSE: This phase II trial is studying how well giving oxaliplatin together with fluorouracil and radiation therapy works in treating patients who are undergoing surgery for stage II or stage III cancer of the esophagus or gastroesophageal junction.


Condition Intervention Phase
Esophageal Cancer
Drug: fluorouracil
Drug: oxaliplatin
Procedure: conventional surgery
Radiation: radiation therapy
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Oxaliplatin (NSC-266046) Plus Protracted Infusion 5-Fluorouracil And Radiation For Potentially Curable Esophageal Cancer: A Phase II Trial With Molecular Correlates

Resource links provided by NLM:


Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:
  • Pathological Complete Response [ Time Frame: 10-16 weeks after beginning study treatment ] [ Designated as safety issue: No ]
    Complete pathologic response assessed after chemoradiotherapy and surgery, defined as no evidence of residual disease on path review. Patients who did not receive surgery are assumed to have not responded.


Secondary Outcome Measures:
  • Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
    Only adverse events that are possibly, probably or definitely related to study drug are reported.

  • Overall Survival [ Time Frame: 0-5 years ] [ Designated as safety issue: No ]
    Measured from time of registration to death, or last contact date

  • Progression-free Survival [ Time Frame: 0-3 years ] [ Designated as safety issue: No ]
    measured from date of registration to time of first documentation of progression by Response Evaluation Criteria in Solid Tumors (RECIST), death, or last contact date.


Enrollment: 98
Study Start Date: September 2004
Study Completion Date: August 2011
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Chemo Plus RT, Surgery, Chemo
neoadjuvant fluorouracil, oxaliplatin and radiation therapy followed by conventional surgery and adjuvant fluoruracil and oxaliplatin
Drug: fluorouracil
Before surgery: 180 mg/m2/day by 24-hour infusion days 8 through 43. After surgery:180 mg/m2/day by 24-hour infusion days 1 through 36.
Other Name: 5-FU
Drug: oxaliplatin
Before surgery: 85 mg/m2 by 2-hour IV infusion days 1, 15, and 29. After surgery: 85 mg/m2 by 2-hour IV infusion days 1, 15, and 29.
Other Name: eloxatin
Procedure: conventional surgery
The surgical technique will depend upon the location and extent of tumor and individual surgeon preference.
Radiation: radiation therapy
Starting Day 8, patients will be treated 5 days/week at 180 centigray (cGy)/day times 25 fractions to a total dose of 4,500 cGy.

Detailed Description:

OBJECTIVES:

Primary

  • Determine the pathologic complete response probability in patients with stage II or III adenocarcinoma of the esophagus or gastroesophageal junction treated with neoadjuvant oxaliplatin, fluorouracil, and radiotherapy followed by definitive surgical resection.

Secondary

  • Determine the frequency and severity of toxic effects associated with this neoadjuvant regimen in these patients.
  • Determine the overall survival and progression-free survival of patients treated with this regimen.

Exploratory Analyses (subject to funding availability)

  • Correlate, preliminarily, initial messenger ribonucleic acid (mRNA) levels of the genes for thymidylate synthase (TS), γ-glutamyl transpeptidase (γGT), γ-glutamyl cysteine (γ-GCS), DNA excision repair cross-complementing (ERCC-1), and xeroderma pigmentosum (XPA) with response and survival of patients treated with this regimen.
  • Correlate, preliminarily, the mRNA levels of TS, γGT, γ-GCS, ERCC-1, and XPA before and after treatment with this regimen with survival of these patients.
  • Correlate, preliminarily, specific genetic polymorphisms of TS and ERCC-1 with tumor response and overall survival of patients treated with this regimen.

OUTLINE: This is a multicenter study.

  • Neoadjuvant chemoradiotherapy: Patients receive oxaliplatin IV over 2 hours on days 1, 15, and 29 and fluorouracil (5-FU) IV continuously on days 8-43. Beginning on day 8, patients also undergo radiotherapy once daily, 5 days a week, for 5 weeks.
  • Surgery: Patients with stable disease or better undergo surgical resection 4-10 weeks after completion of chemoradiotherapy.
  • Adjuvant chemotherapy: Beginning 4-10 weeks after surgery, patients receive chemotherapy comprising oxaliplatin IV over 2 hours on days 1, 15, and 29 and 5-FU IV continuously on days 1-36.

Treatment continues in the absence of unacceptable toxicity or disease progression.

Patients are followed every 3 months for 1 year and then every 6 months for 2 years.

PROJECTED ACCRUAL: A total of 45-85 patients will be accrued for this study within 17-21 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed primary adenocarcinoma of the thoracic esophagus or gastroesophageal junction

    • No recurrent disease
    • Primary esophageal tumor at least 20 cm below the incisors (if < 26 cm below the incisors, a bronchoscopy must be performed and cytology must be negative)
    • Esophageal disease confined to esophagus and peri-esophageal soft tissue
    • Gastroesophageal junction disease extending ≤ 2 cm into the gastric cardia
  • Clinical stage II or III disease by CT scan or MRI

    • If no esophageal mass is detected by these methods, esophageal endoscopic ultrasound is required to determine stage
    • Positron-emission tomography scan is required to confirm stage
  • Measurable or non-measurable disease by x-ray, scanning, or physical examination
  • No celiac axis nodes ≥ 1.5 cm

    • Measurable regional lymph nodes ≥ 1.5 cm at stations 2-10=N1 OR subdiaphragmatic lymph nodes at stations 15-19 ≤ 1.5 cm by CT scan or MRI allowed
    • Palpable supraclavicular lymph nodes must be free of metastatic esophageal cancer by biopsy

PATIENT CHARACTERISTICS:

Age

  • Over 18

Performance status

  • Zubrod 0-2

Life expectancy

  • Not specified

Hematopoietic

  • Absolute neutrophil count ≥ 1,500/mm^3
  • White blood cell (WBC) count ≥ 3,000/mm^3
  • Hemoglobin ≥ 10.0 g/dL (transfusion allowed)

Hepatic

  • Albumin ≥ 3 g/dL
  • Bilirubin normal

Renal

  • Creatinine ≤ 1.5 times upper limit of normal

Cardiovascular

  • No myocardial infarction or cerebrovascular event within the past 6 months

Pulmonary

  • No active pneumonia or inflammatory lung infiltrate

Other

  • No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
  • No peripheral neuropathy ≥ grade 2
  • Not pregnant or nursing
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • No prior chemotherapy for esophageal cancer

Endocrine therapy

  • Not specified

Radiotherapy

  • No prior radiotherapy for esophageal cancer
  • No concurrent intensity-modulated radiotherapy

Surgery

  • No prior surgical resection or attempted surgical resection of esophageal cancer
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00086996

  Show 143 Study Locations
Sponsors and Collaborators
Southwest Oncology Group
Investigators
Study Chair: Lawrence P. Leichman, MD Desert Regional Medical Center Comprehensive Cancer Center
Study Chair: Charles R. Thomas, MD OHSU Knight Cancer Institute
  More Information

Additional Information:
Publications:
Leichman L, Goldman BH, Benedetti JK, et al.: Oxaliplatin (OXP) plus protracted infusion 5-fluorouracil (PIFU) and external beam radiation (EBRT) prior to surgery (S) for potentially curable esophageal adenocarcinoma (EA): A Southwest Oncology Group (SWOG) phase II trial with molecular correlates (S0356). [Abstract] J Clin Oncol 27 (Suppl 15): A-4513, 2009.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT00086996     History of Changes
Other Study ID Numbers: CDR0000371963, U10CA032102, S0356
Study First Received: July 8, 2004
Results First Received: March 5, 2012
Last Updated: September 4, 2013
Health Authority: United States: Federal Government

Keywords provided by Southwest Oncology Group:
adenocarcinoma of the esophagus
stage II esophageal cancer
stage III esophageal cancer

Additional relevant MeSH terms:
Esophageal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Fluorouracil
Oxaliplatin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 24, 2014